PL209572B1 - Kompozycja farmaceutyczna zawierająca podstawione azaindole, podstawione azaindole i ich farmaceutyczne zastosowania - Google Patents

Info

Publication number

PL209572B1

PL209572B1 PL355819A PL35581900A PL209572B1 PL 209572 B1 PL209572 B1 PL 209572B1 PL 355819 A PL355819 A PL 355819A PL 35581900 A PL35581900 A PL 35581900A PL 209572 B1 PL209572 B1 PL 209572B1

Authority

PL

Poland

Prior art keywords

pyrrolo

methyl

compound

compounds

pyrazin

Prior art date

1999-12-24

Links

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• Global Dossier
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• 125000005334 azaindolyl group Chemical group N1N=C(C2=CC=CC=C12)* 0.000 title claims description 15
• 150000001875 compounds Chemical class 0.000 claims abstract description 406
• 239000000203 mixture Substances 0.000 claims abstract description 163
• 150000003839 salts Chemical class 0.000 claims abstract description 68
• 125000000217 alkyl group Chemical group 0.000 claims abstract description 54
• 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 49
• 239000001257 hydrogen Substances 0.000 claims abstract description 42
• 125000004435 hydrogen atom Chemical class [H]* 0.000 claims abstract description 7
• -1 hydroxy, phenyl Chemical group 0.000 claims description 89
• 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 48
• 238000011282 treatment Methods 0.000 claims description 41
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 25
• 239000003814 drug Substances 0.000 claims description 25
• 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 23
• 229910052799 carbon Inorganic materials 0.000 claims description 22
• 108091000080 Phosphotransferase Proteins 0.000 claims description 21
• 102000020233 phosphotransferase Human genes 0.000 claims description 21
• 229910052736 halogen Inorganic materials 0.000 claims description 18
• 150000002367 halogens Chemical group 0.000 claims description 18
• 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 17
• 230000002401 inhibitory effect Effects 0.000 claims description 14
• 206010028980 Neoplasm Diseases 0.000 claims description 13
• 150000002431 hydrogen Chemical group 0.000 claims description 12
• 238000004519 manufacturing process Methods 0.000 claims description 12
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 11
• 206010003246 arthritis Diseases 0.000 claims description 9
• MIJMZVTYIXYSDK-UHFFFAOYSA-N 6-(5-methoxy-1-methylindol-3-yl)-5h-pyrrolo[2,3-b]pyrazine Chemical compound C1=CN=C2NC(C3=CN(C)C4=CC=C(C=C43)OC)=CC2=N1 MIJMZVTYIXYSDK-UHFFFAOYSA-N 0.000 claims description 8
• 125000003406 indolizinyl group Chemical group C=1(C=CN2C=CC=CC12)* 0.000 claims description 8
• 125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims description 7
• 201000011510 cancer Diseases 0.000 claims description 7
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 7
• 239000008194 pharmaceutical composition Substances 0.000 claims description 7
• XQYJBGKMIPFFJS-UHFFFAOYSA-N 6-(4-methoxyphenyl)-5h-pyrrolo[2,3-b]pyrazine Chemical compound C1=CC(OC)=CC=C1C1=CC2=NC=CN=C2N1 XQYJBGKMIPFFJS-UHFFFAOYSA-N 0.000 claims description 6
• 208000022559 Inflammatory bowel disease Diseases 0.000 claims description 6
• 201000004681 Psoriasis Diseases 0.000 claims description 6
• 208000006673 asthma Diseases 0.000 claims description 6
• 125000001041 indolyl group Chemical group 0.000 claims description 6
• 125000003831 tetrazolyl group Chemical group 0.000 claims description 6
• 239000004480 active ingredient Substances 0.000 claims description 5
• 239000000546 pharmaceutical excipient Substances 0.000 claims description 5
• ONJMAXYFHBVNTH-UHFFFAOYSA-N 6-phenyl-5h-pyrrolo[2,3-b]pyrazine Chemical compound N1C2=NC=CN=C2C=C1C1=CC=CC=C1 ONJMAXYFHBVNTH-UHFFFAOYSA-N 0.000 claims description 4
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 4
• 125000001544 thienyl group Chemical group 0.000 claims description 4
• BEVMNJLOWZOCEF-UHFFFAOYSA-N 2-methyl-6-phenyl-5h-pyrrolo[2,3-b]pyrazine Chemical compound C=1C2=NC(C)=CN=C2NC=1C1=CC=CC=C1 BEVMNJLOWZOCEF-UHFFFAOYSA-N 0.000 claims description 3
• WOSGPBFDGVRZKT-UHFFFAOYSA-N 3-methyl-6-phenyl-5h-pyrrolo[2,3-b]pyrazine Chemical compound N1C2=NC(C)=CN=C2C=C1C1=CC=CC=C1 WOSGPBFDGVRZKT-UHFFFAOYSA-N 0.000 claims description 3
• YGINNQXWHUWSHG-UHFFFAOYSA-N 6-(2-chlorophenyl)-5h-pyrrolo[2,3-b]pyrazine Chemical compound ClC1=CC=CC=C1C1=CC2=NC=CN=C2N1 YGINNQXWHUWSHG-UHFFFAOYSA-N 0.000 claims description 3
• VFKHBJJSGUYSDC-UHFFFAOYSA-N 6-(4-chlorophenyl)-5h-pyrrolo[2,3-b]pyrazine Chemical compound C1=CC(Cl)=CC=C1C1=CC2=NC=CN=C2N1 VFKHBJJSGUYSDC-UHFFFAOYSA-N 0.000 claims description 3
• QLBVJDQLXOSSMT-UHFFFAOYSA-N 7-methyl-6-phenyl-5h-pyrrolo[2,3-b]pyrazine Chemical compound N1C2=NC=CN=C2C(C)=C1C1=CC=CC=C1 QLBVJDQLXOSSMT-UHFFFAOYSA-N 0.000 claims description 3
• UGHVSNVFYBZSLH-UHFFFAOYSA-N [1-[1-methyl-3-(5h-pyrrolo[2,3-b]pyrazin-6-yl)indol-5-yl]oxycyclobutyl]methanol Chemical compound C=1C=C2N(C)C=C(C=3NC4=NC=CN=C4C=3)C2=CC=1OC1(CO)CCC1 UGHVSNVFYBZSLH-UHFFFAOYSA-N 0.000 claims description 3
• 125000003277 amino group Chemical group 0.000 claims description 3
• 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 3
• 239000003937 drug carrier Substances 0.000 claims description 3
• 125000002541 furyl group Chemical group 0.000 claims description 3
• 125000002883 imidazolyl group Chemical group 0.000 claims description 3
• 208000027866 inflammatory disease Diseases 0.000 claims description 3
• 125000002183 isoquinolinyl group Chemical group C1(=NC=CC2=CC=CC=C12)* 0.000 claims description 3
• 125000004076 pyridyl group Chemical group 0.000 claims description 3
• 125000000168 pyrrolyl group Chemical group 0.000 claims description 3
• 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 claims description 3
• GOJUJUVQIVIZAV-UHFFFAOYSA-N 2-amino-4,6-dichloropyrimidine-5-carbaldehyde Chemical group NC1=NC(Cl)=C(C=O)C(Cl)=N1 GOJUJUVQIVIZAV-UHFFFAOYSA-N 0.000 claims description 2
• 150000001299 aldehydes Chemical class 0.000 claims description 2
• 238000002560 therapeutic procedure Methods 0.000 claims description 2
• 125000006656 (C2-C4) alkenyl group Chemical group 0.000 claims 1
• GDTFIRYHAYIXIP-UHFFFAOYSA-N methoxycyclobutane Chemical group COC1CCC1 GDTFIRYHAYIXIP-UHFFFAOYSA-N 0.000 claims 1
• VXPLXMJHHKHSOA-UHFFFAOYSA-N propham Chemical group CC(C)OC(=O)NC1=CC=CC=C1 VXPLXMJHHKHSOA-UHFFFAOYSA-N 0.000 claims 1
• 125000003118 aryl group Chemical group 0.000 abstract description 22
• 125000001072 heteroaryl group Chemical group 0.000 abstract description 19
• 229940002612 prodrug Drugs 0.000 abstract description 16
• 239000000651 prodrug Substances 0.000 abstract description 16
• 239000012453 solvate Substances 0.000 abstract description 10
• 125000004093 cyano group Chemical group *C#N 0.000 abstract description 9
• 102000001253 Protein Kinase Human genes 0.000 abstract description 8
• 125000003342 alkenyl group Chemical group 0.000 abstract description 8
• 108060006633 protein kinase Proteins 0.000 abstract description 8
• 125000005843 halogen group Chemical group 0.000 abstract description 7
• 125000002252 acyl group Chemical group 0.000 abstract description 4
• 125000000592 heterocycloalkyl group Chemical group 0.000 abstract description 3
• 125000001424 substituent group Chemical group 0.000 abstract description 3
• 229910014033 C-OH Inorganic materials 0.000 abstract 1
• 229910014570 C—OH Inorganic materials 0.000 abstract 1
• 125000001475 halogen functional group Chemical group 0.000 abstract 1
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 384
• 238000000034 method Methods 0.000 description 235
• 239000007787 solid Substances 0.000 description 232
• 239000000243 solution Substances 0.000 description 178
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 165
• WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 142
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 125
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 118
• ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 108
• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 92
• YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 71
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 68
• CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 68
• 239000011541 reaction mixture Substances 0.000 description 63
• 238000005481 NMR spectroscopy Methods 0.000 description 56
• OFBQJSOFQDEBGM-UHFFFAOYSA-N Pentane Chemical compound CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 54
• 210000004027 cell Anatomy 0.000 description 53
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 52
• 239000002253 acid Substances 0.000 description 51
• 238000004128 high performance liquid chromatography Methods 0.000 description 51
• ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 45
• 238000003756 stirring Methods 0.000 description 44
• 239000000377 silicon dioxide Substances 0.000 description 42
• 210000004072 lung Anatomy 0.000 description 41
• IMNFDUFMRHMDMM-UHFFFAOYSA-N anhydrous n-heptane Natural products CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 40
• HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 39
• 238000004809 thin layer chromatography Methods 0.000 description 39
• WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 36
• 238000006243 chemical reaction Methods 0.000 description 34
• 229910052943 magnesium sulfate Inorganic materials 0.000 description 34
• 235000019341 magnesium sulphate Nutrition 0.000 description 34
• YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 33
• 239000000427 antigen Substances 0.000 description 32
• 108091007433 antigens Proteins 0.000 description 32
• 102000036639 antigens Human genes 0.000 description 32
• 239000012267 brine Substances 0.000 description 28
• 230000000694 effects Effects 0.000 description 28
• HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 28
• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 27
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 27
• 230000005764 inhibitory process Effects 0.000 description 26
• VAJOSPMTARTPKN-UHFFFAOYSA-N 2-[5-methoxy-3-(5h-pyrrolo[2,3-b]pyrazin-6-yl)indol-1-yl]-1-morpholin-4-ylethanone Chemical compound C1=C(C=2NC3=NC=CN=C3C=2)C2=CC(OC)=CC=C2N1CC(=O)N1CCOCC1 VAJOSPMTARTPKN-UHFFFAOYSA-N 0.000 description 24
• 230000000875 corresponding effect Effects 0.000 description 23
• 239000012442 inert solvent Substances 0.000 description 23
• 239000002904 solvent Substances 0.000 description 23
• MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 22
• PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 22
• 230000002829 reductive effect Effects 0.000 description 22
• 238000010992 reflux Methods 0.000 description 22
• 229910052938 sodium sulfate Inorganic materials 0.000 description 22
• 235000011152 sodium sulphate Nutrition 0.000 description 22
• 108010058846 Ovalbumin Proteins 0.000 description 20
• 239000000284 extract Substances 0.000 description 20
• 239000012299 nitrogen atmosphere Substances 0.000 description 20
• 229940092253 ovalbumin Drugs 0.000 description 20
• UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 19
• 241000700159 Rattus Species 0.000 description 18
• 150000001721 carbon Chemical group 0.000 description 18
• UAOMVDZJSHZZME-UHFFFAOYSA-N diisopropylamine Chemical compound CC(C)NC(C)C UAOMVDZJSHZZME-UHFFFAOYSA-N 0.000 description 18
• VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 18
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 17
• 241001465754 Metazoa Species 0.000 description 17
• 239000002585 base Substances 0.000 description 17
• 239000000725 suspension Substances 0.000 description 17
• 108090000461 Aurora Kinase A Proteins 0.000 description 16
• 102100032311 Aurora kinase A Human genes 0.000 description 16
• 102000016621 Focal Adhesion Protein-Tyrosine Kinases Human genes 0.000 description 16
• 108010067715 Focal Adhesion Protein-Tyrosine Kinases Proteins 0.000 description 16
• XBDQKXXYIPTUBI-UHFFFAOYSA-N Propionic acid Chemical class CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 16
• 239000010410 layer Substances 0.000 description 16
• 210000001519 tissue Anatomy 0.000 description 16
• IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 15
• 238000003818 flash chromatography Methods 0.000 description 15
• 229910052757 nitrogen Inorganic materials 0.000 description 15
• WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 14
• INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 14
• 238000000746 purification Methods 0.000 description 14
• 230000004044 response Effects 0.000 description 14
• 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 description 13
• QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 13
• 150000001204 N-oxides Chemical class 0.000 description 13
• KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 13
• KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 13
• 229940079593 drug Drugs 0.000 description 13
• 239000002609 medium Substances 0.000 description 13
• 239000012074 organic phase Substances 0.000 description 13
• 239000012312 sodium hydride Substances 0.000 description 13
• 229910000104 sodium hydride Inorganic materials 0.000 description 13
• WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 12
• BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 12
• KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 12
• 239000012634 fragment Substances 0.000 description 12
• BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 12
• 239000003921 oil Substances 0.000 description 12
• 235000019198 oils Nutrition 0.000 description 12
• 230000008569 process Effects 0.000 description 12
• BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 11
• 238000012360 testing method Methods 0.000 description 11
• WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 10
• NTYJJOPFIAHURM-UHFFFAOYSA-N Histamine Chemical compound NCCC1=CN=CN1 NTYJJOPFIAHURM-UHFFFAOYSA-N 0.000 description 10
• WTDHULULXKLSOZ-UHFFFAOYSA-N Hydroxylamine hydrochloride Chemical compound Cl.ON WTDHULULXKLSOZ-UHFFFAOYSA-N 0.000 description 10
• GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 10
• 229910052794 bromium Inorganic materials 0.000 description 10
• 150000002148 esters Chemical class 0.000 description 10
• 239000000706 filtrate Substances 0.000 description 10
• RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 10
• SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical class C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 description 9
• 229920005654 Sephadex Polymers 0.000 description 9
• 239000012507 Sephadex™ Substances 0.000 description 9
• 238000011685 brown norway rat Methods 0.000 description 9
• 239000006071 cream Substances 0.000 description 9
• 238000000921 elemental analysis Methods 0.000 description 9
• 238000001914 filtration Methods 0.000 description 9
• 239000012458 free base Substances 0.000 description 9
• 150000004677 hydrates Chemical class 0.000 description 9
• 239000011259 mixed solution Substances 0.000 description 9
• 239000002244 precipitate Substances 0.000 description 9
• CHIFTAQVXHNVRW-UHFFFAOYSA-N 1h-indole-3-carbonitrile Chemical compound C1=CC=C2C(C#N)=CNC2=C1 CHIFTAQVXHNVRW-UHFFFAOYSA-N 0.000 description 8
• MVXVYAKCVDQRLW-UHFFFAOYSA-N 1h-pyrrolo[2,3-b]pyridine Chemical compound C1=CN=C2NC=CC2=C1 MVXVYAKCVDQRLW-UHFFFAOYSA-N 0.000 description 8
• ZKHQWZAMYRWXGA-UHFFFAOYSA-N Adenosine triphosphate Natural products C1=NC=2C(N)=NC=NC=2N1C1OC(COP(O)(=O)OP(O)(=O)OP(O)(O)=O)C(O)C1O ZKHQWZAMYRWXGA-UHFFFAOYSA-N 0.000 description 8
• NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 8
• HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 8
• ROSDSFDQCJNGOL-UHFFFAOYSA-N Dimethylamine Chemical compound CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 description 8
• YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 8
• FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 8
• JFDZBHWFFUWGJE-UHFFFAOYSA-N benzonitrile Chemical compound N#CC1=CC=CC=C1 JFDZBHWFFUWGJE-UHFFFAOYSA-N 0.000 description 8
• 125000000118 dimethyl group Chemical group [H]C([H])([H])* 0.000 description 8
• 231100000673 dose–response relationship Toxicity 0.000 description 8
• 125000004494 ethyl ester group Chemical group 0.000 description 8
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 8
• 239000000543 intermediate Substances 0.000 description 8
• CAWHJQAVHZEVTJ-UHFFFAOYSA-N methylpyrazine Chemical compound CC1=CN=CC=N1 CAWHJQAVHZEVTJ-UHFFFAOYSA-N 0.000 description 8
• 239000002480 mineral oil Substances 0.000 description 8
• 235000010446 mineral oil Nutrition 0.000 description 8
• 210000000440 neutrophil Anatomy 0.000 description 8
• NFHFRUOZVGFOOS-UHFFFAOYSA-N palladium;triphenylphosphane Chemical compound [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 NFHFRUOZVGFOOS-UHFFFAOYSA-N 0.000 description 8
• XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 8
• GETQZCLCWQTVFV-UHFFFAOYSA-N trimethylamine Chemical compound CN(C)C GETQZCLCWQTVFV-UHFFFAOYSA-N 0.000 description 8
• KYWSGFFFDGCSES-UHFFFAOYSA-N 1-methyl-3-(5h-pyrrolo[2,3-b]pyrazin-6-yl)indol-5-ol Chemical compound C12=CC(O)=CC=C2N(C)C=C1C1=CC2=NC=CN=C2N1 KYWSGFFFDGCSES-UHFFFAOYSA-N 0.000 description 7
• YYROPELSRYBVMQ-UHFFFAOYSA-N 4-toluenesulfonyl chloride Chemical compound CC1=CC=C(S(Cl)(=O)=O)C=C1 YYROPELSRYBVMQ-UHFFFAOYSA-N 0.000 description 7
• ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical group [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 7
• 239000006146 Roswell Park Memorial Institute medium Substances 0.000 description 7
• 102000000551 Syk Kinase Human genes 0.000 description 7
• 108010016672 Syk Kinase Proteins 0.000 description 7
• 108010073929 Vascular Endothelial Growth Factor A Proteins 0.000 description 7
• 102000005789 Vascular Endothelial Growth Factors Human genes 0.000 description 7
• 108010019530 Vascular Endothelial Growth Factors Proteins 0.000 description 7
• 229960000583 acetic acid Drugs 0.000 description 7
• WNROFYMDJYEPJX-UHFFFAOYSA-K aluminium hydroxide Chemical compound [OH-].[OH-].[OH-].[Al+3] WNROFYMDJYEPJX-UHFFFAOYSA-K 0.000 description 7
• 125000003710 aryl alkyl group Chemical group 0.000 description 7
• 239000003054 catalyst Substances 0.000 description 7
• 125000000753 cycloalkyl group Chemical group 0.000 description 7
• 239000006185 dispersion Substances 0.000 description 7
• 210000003979 eosinophil Anatomy 0.000 description 7
• 230000014509 gene expression Effects 0.000 description 7
• 229910052740 iodine Inorganic materials 0.000 description 7
• 239000003960 organic solvent Substances 0.000 description 7
• 238000002360 preparation method Methods 0.000 description 7
• 229920006395 saturated elastomer Polymers 0.000 description 7
• 229910000030 sodium bicarbonate Inorganic materials 0.000 description 7
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